Sterile packaging unit and method for poducing same

ABSTRACT

A sterile packaging unit includes a disposable bioprocessing component ( 20 ) and a packaging ( 30 ). The disposable bioprocessing component ( 20 ) has a component wall that encloses a processing space and on which is secured a sensor system ( 40 ) with at least one sensor head (T, P, I, L, D) and with attached sensor electronics ( 42 ) that include a memory unit ( 44 ). The packaging ( 30 ) hermetically encloses the disposable bioprocessing component ( 20 ) and has a flexible packaging wall. The disposable bioprocessing component ( 20 ) and the packaging ( 30 ). are sterilized by being jointly irradiated with ionizing radiation. The sensor electronics ( 42 ) are connected electrically to a contact unit ( 34 ) extending through the packaging wall.

BACKGROUND Field of the Invention

The present invention relates to a sterile packaging unit, comprising

-   -   a disposable bioprocessing component with a component wall which        encloses a processing space and on which is secured a sensor        system with at least one sensor head and with attached sensor        electronics comprising a memory unit, and    -   a packaging which hermetically encloses the disposable        bioprocessing component, which are sterilized by being jointly        irradiated with ionizing radiation.

Furthermore, the invention relates to a method for producing suchpackaging unit, comprising the following steps:

-   -   Providing a disposable bioprocessing component with a component        wall which encloses a processing space and on which is secured a        sensor system with at least one sensor head and with attached        sensor electronics comprising a memory unit,    -   Hermetically enclosing the disposable bioprocessing component        with a packaging and    -   Sterilizing disposable bioprocessing component and packaging by        joint irradiation with ionizing radiation.

Description of the Related Art

U.S. Pat. No. 8,963,684 B2 provides an example of known disposablebioprocessing components.

In the context of the present description, the term bioprocessingcomponent means any component of a system for carrying out bioprocesses.Bioprocessing components with a component wall enclosing a processingspace are any kind of receptacles and passages that are suitable for usein bioprocessing systems. These include, in particular: storagecontainers, bioreactor containers, hoses, valves, pipelines, etc.

In modern pharmaceutical and biotechnology manufacturing methods,disposable components are increasingly used. They can be economicallymanufactured and—unlike reusable components—do not require expensivecleaning and sterilization after every use. In particular, flexibleplastic bags, which may be used as bioreactors or storage containers forbioreactive fluids, for example, are a principal subject of the presentinvention, even though rigid-wall containers may also be used inaccordance with the invention. However, it goes without saying that thepresent invention also relates to other bioprocessing components whichare configured for disposable use, such as: hoses, valves, pipelines,etc. To simplify the explanations given below, reference is frequentlymade just to said bags. The person skilled in the art will neverthelessunderstand that the corresponding statements, unless expressly statedotherwise, are also applicable to other types of disposablebioprocessing components.

The aforementioned publication discloses disposable bioprocessingcomponents of this type, which in each case have a sensor system that issecured to the component wall. A sensor head is thus in contact with theprocessing space and is electrically connected to sensor electronics,which have, among other things, a memory unit. The memory unit isconfigured as a ferroelectric random access memory (FRAM) in order to beresistant to gamma radiation, which is typically used for thesterilization of the disposable bioprocessing components. Sensor datacan be read into the memory unit. A transponder represents an interfacebetween the memory unit and an external peripheral device so that datacan be read into the memory unit from outside via the transponder andcan be read out from the memory unit to the outside. The manufacturingmethod for such a disposable bioprocessing component that is describedin said publication provides for sterilizing the component using gammairradiation and activating the sensor electronics after thesterilization step in order to read calibration data into the memoryunit. In this process, one may take into account the state of the sensorsystem, which may have been changed from its original state by theexposure during the gamma sterilization. Alternatively or additionally,it is possible to read additional data, e.g., identification data, fromoutside into the memory unit. Thus, the sensor electronics are activatedin any event by supplying power via the transponder by means of anelectromagnetic high-frequency field.

The person skilled in the art knows that such sterile disposablebioprocessing components, in and of themselves, do not constitutesellable products, because contamination would come in again veryquickly during storage and handling of the “bare” disposablebioprocessing component. As the person skilled in the art knows, it istherefore absolutely necessary to prepare packaging units from saiddisposable bioprocessing component and a packaging that hermeticallyencloses it. In this arrangement, typically and—also within the contextof the present invention—preferably, packaging with a flexible packagingwall, in particular flexible plastic bags, are used. The packaging takesplace before the sterilization so that packaging and disposablebioprocessing components are jointly irradiated with ionizing radiation(e.g. beta, gamma or x-ray radiation) during the sterilization step andare thereby sterilized. Although the outer side of the packagingundergoes contamination again during further storage and handling, thedisposable bioprocessing component hermetically enclosed by thepackaging remains sterile. The generic name “sterile packaging unit”that is used here, which by no means also assumes sterility of thepackaging outer side, should also be understood in this sense.

It is disadvantageous in the case of the known packaging units thatreading data into the memory unit always requires a close physicalproximity of the sensor electronics, in particular of the transponder,to an external read-in/read-out unit, which supplies the power for thesensor system in particular via an applied electromagnetichigh-frequency field.

The present invention seeks to solve the problem of improving a genericpackaging unit and a method for manufacturing the unit in such a waythat the sensor electronics can be continuously active even during thestorage times of the packaging unit.

SUMMARY

The invention relates to a sterile packaging unit that includes adisposable bioprocessing component and a packaging. The disposablebioprocessing component has a component wall that encloses a processingspace and on which a sensor system is secured with at least one sensorhead and with attached sensor electronics that include a memory unit.The packaging hermetically encloses the disposable bioprocessingcomponent and has a flexible packaging wall. The disposablebioprocessing component and the packaging are sterilized by beingjointly irradiated with ionizing radiation. The sensor electronics areelectrically connected to a contact unit extending through the packagingwall.

The invention also relates to a method for producing a sterile packagingunit. The method includes providing a disposable bioprocessing componentwith a component wall that encloses a processing space and on which issecured a sensor system with at least one sensor head and with attachedsensor electronics that include a memory unit. The method also includeshermetically closing the disposable bioprocessing component with apackaging and then sterilizing the disposable bioprocessing componentand the packaging by joint irradiation with ionizing radiation. Themethod further includes electrically connecting the sensor electronicsto a contact unit extending through the packaging wall, and the contactunit is connected to an electrical energy storage after thesterilization step.

The invention provides a possibility of durably connecting the sensorelectronics to a power source. The obvious measure of integrating abattery in the sensor electronics themselves is out of the questionbecause of the irradiation with ionizing radiation that is required forthe sterilization.

The invention therefore takes a different route and provides anelectrical connection between the sensor electronics (on the disposablebioprocessing component) and the packaging, wherein a contact unit ofthis electrical connection extends through the packaging wall, so thatthe sensor electronics are electrically accessible from outside of thepackaging. The person skilled in the art knows techniques on how toapply an electrical conductor in order to, on the one hand, electricallyextend through a packaging wall and, on the other hand, not reduce itshermetic protective effect. For example, electrically conductive contactpads can be welded or glued into the packaging wall of a plastic bag.

The electrical accessibility of the sensor electronics from the outsidethat is created in this way makes it possible to connect a battery or,in general, an electrical energy storage to the sensor electronics onlyafter sterilization by ionizing radiation. On the one hand, theelectrical energy storage is not damaged during the irradiation; on theother hand, there is no reason to fear contamination of the disposablebioprocessing components within the context of attaching the electricalenergy storage because the latter does not come into contact with thepackaging interior.

The contact unit may terminate in a pocket of the packaging wall that isaccessible from the outside. In the region of the pocket, the packagingwall therefore has a double-wall design, an inner wall serving toprotect the packaging contents and a contact unit extends through it,while the outer packaging wall serves exclusively for the mounting andprotection of the electrical energy storage.

The embodiment of the packaging unit according to the invention opens anumber of new possibilities of use. The person skilled in the art willrecognize that the use of the one-time writing of calibration andidentification data into the memory known from the publication discussedat the outset is easily possible also in the case of the packaging unitaccording to the invention. However, the continuous activation of thesensor electronics by the continuously connected power source enablesother forms of use, in particular with regard to recording a history ofthe disposable bioprocessing component during its lifetime betweenproduction and use.

The sensor system may comprise an electrically readable dosimeter. Thisdosimeter passively records—i.e. without an electrical power supplybeing required—the radiation exposure during the sterilization process.The control electronics may further comprise a control unit that isconfigured to read the dosimeter automatically after contacting of theelectrical energy storage and to write a read-out dose value into thememory unit automatically, it is possible to check at a later timewhether the radiation dose was sufficient for a sterilization or whetherthe radiation dose was perhaps too high for sensitive elements of thesensor system. This information may, on the one hand, be used as anelement of quality management for comprehensive or random-samplechecking of the sterilization efficiency before storage of the packagingunits. Alternatively or additionally, it can also be used immediatelybefore the use of the disposable bioprocessing component to check itsviability.

Because of the continuous supply of power to the sensor system, a nearlyseamless monitoring of the storage history of the packaging unit ispossible. The sensor system also may comprise at least one environmentalparameter sensor and the sensor electronics comprise a control unit thatis configured to periodically read the environmental parameter sensorafter contacting of the electrical energy storage and to write read-outparameter values together with the corresponding reading time stampsinto the memory unit. Some examples of environmental parameter sensorsinclude temperature, pressure and humidity sensors. While the formercomprise environmental parameters that act directly on the bioprocessingcomponent and can affect their service life, a humidity sensor can beused to detect possible leaks in the packaging that in the intact state,because of the packaging's hermetic enclosure effect, really should notpermit any humidity fluctuations in the region of the sensor system. Inthe present context, the concept of the environmental parameter sensorshould be understood more broadly and can in particular also includesensor systems that interact via transponder technology, for example,with external beacons and record storage positions, for example.

Additional features and advantages of the invention are evident from thefollowing special description and the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic representation of a packaging unit in accordancewith the invention.

DETAILED DESCRIPTION

FIG. 1 shows an embodiment of a packaging unit 10 according to theinvention in a simplified schematic illustration. This embodimentcomprises a disposable bioreactor bag 20 and a packaging enclosure 30that hermetically encloses the disposable bioreactor bag 20. Thedisposable bioreactor bag 20 supports on its bag wall a sensor system 40having five sensor heads T, P, I, L, D and having sensor electronics 42that comprise, in particular, a memory unit 44 configured as FRAM aswell as a control unit 46. The sensor heads T, P, I, L, D are connectedto the memory unit 44 via a control unit 46. In the depicted embodiment,sensor T is a temperature sensor for the measurement of a temperature inthe interior or exterior of the disposable bioreactor bag 20. Sensor Pis a pressure sensor for the measurement of a pressure inside or outsideof the disposable bioreactor bag 20. Sensor I is an internal sensor formeasuring a parameter in the interior of the bioreactor bag 20, e.g.,the pH value of a fluid present in the interior of the bioreactor bag 20during the use of the latter. The sensor L is a location sensor that iscapable of communicating with an external locator beacon BL duringoperation. Sensor D is a passively operating, electrically readabledosimeter that in the passive state is suitable for detecting radiation,in particular gamma radiation, the amount of which in the active statecan then be electrically read.

The outer wall of the packaging enclosure 30 is provided with a pocket32 in which is arranged an electrical energy storage 50, for example alithium ion rechargeable battery. In the shown embodiment, the pocket 32is provided with a sealable cover 33 for the protection of theelectrical energy storage 50. The electrical energy storage 50 is inelectrical contact with a contact pad 34, which is preferably integrallyjoined to the wall of the packaging enclosure 30 and extends through it.Inside the packaging enclosure 30, the contact pad 34 contacts aconductor 36, which is connected at its other end to the sensorelectronics 42 of Sensor 40 so that the electrical energy storagesupplies the sensor system 40 with the power required for its operation.

Provided for the production of the packaging unit 10 according to theinvention are, first, the bioreactor bag 20 along with sensor system 40and packaging enclosure 30. Thereafter, the bioreactor bag 20 isinserted in the packaging enclosure 30, and its sensor system 40 isconnected via the conductor 36 to the contact pad 34. Then, thepackaging enclosure 30 is hermetically sealed. The unit preconfigured inthis way undergoes sterilization by being irradiated with ionizingradiation, the amount of radiation being recorded by the passivelyoperating dosimeter D. Following the irradiation, the electrical energystorage 50 is inserted in the pocket 32 and an electrical connection tocontact pad 34 is produced. In this way, the sensor system 40 issupplied with power. The reading of the dosimeter is controlled by thecontrol unit 46, and its recorded dose value is read into the memoryunit 44. Next, the control unit 46 periodically activates Sensors T, Pand L in order to record the corresponding environmental parameters andalso to read them into the memory unit 44 together with the measurementtime stamps. In this manner, a continuous storage history of thepackaging unit 10 is stored in the memory unit 44.

Of course, the embodiments discussed in the specific description andshown in the figures are merely illustrative exemplary embodiments ofthe present invention. In light of this disclosure, the person skilledin the art is given a wide range of possible variations. In particular,the person skilled in the art will recognize that the connectionaccording to the invention of the sensor electronics 42 to the exteriorof the packaging unit 10 can serve not just to supply power to thesensor system 40; it is also possible to additionally implement a datacommunication channel via which data can be read from the memory unit 44or written into it.

LIST OF REFERENCE NUMBERS

-   10 packaging unit-   20 bioreactor bag-   30 packaging-   32 pocket-   33 cover of 32-   34 contact pad-   36 electrical conductor-   40 sensor system-   42 sensor electronics-   44 memory unit-   46 control unit-   50 electrical energy storage-   D dosimeter-   T temperature sensor-   P pressure sensor-   I internal sensor-   L location sensor-   BL locator beacon

1. A sterile packaging unit, comprising a disposable bioprocessingcomponent (20) with a component wall which encloses a processing spaceand on which is secured a sensor (40) with at least one sensor head (T,P, I, L, D) and with attached sensor electronics (42) comprising amemory unit (44), and a packaging (30) that hermetically encloses thedisposable bioprocessing component (20), the disposable bioprocessingcomponent (20) and the packaging (30) being sterilized by being jointlyirradiated with ionizing radiation, wherein: the sensor electronics (42)are electrically connected to a contact unit (34) extending through thepackaging wall.
 2. The packaging unit according to claim 1, wherein: thecontact unit (34) terminates in a pocket accessible from outside (32) ofthe packaging wall.
 3. The packaging unit according to any of thepreceding claim 1, wherein: the contact unit (34) is electricallyconnected to an electrical energy storage (50).
 4. The packaging unitaccording to claim 1, wherein: the sensor system (40) comprises anelectrically readable dosimeter (D).
 5. The packaging unit according toclaim 4, wherein: the sensor electronics (42) comprise a control unit(46) that is configured, after contacting the electrical energy storage(50), to read the dosimeter (D) and write a read-out dose value into thememory unit (44).
 6. The packaging unit according to claim 1, wherein:the sensor system (40) comprises at least one environmental parametersensor (T, P, L) and the sensor electronics (42) comprises a controlunit (46) that is configured, after contacting of the electrical energystorage (50), to periodically read the environmental parameter sensor(T, P, L)electrical energy storage and to write read-out parametervalues into the memory unit (44) together with the corresponding readingtime stamps.
 7. A method for producing a sterile packaging unit (10),comprising the following steps: providing a disposable bioprocessingcomponent (20) with a component wall which encloses a processing spaceand on which is secured a sensor system (40) with at least one sensorhead (T, P, I, L, D) and with attached sensor electronics (42)comprising a memory unit (44), hermetically enclosing the disposablebioprocessing component (20) with a packaging (30) and sterilizing thedisposable bioprocessing component (20) and packaging (30) by jointirradiation with ionizing radiation, and, after the sterilizing step,the method further comprising: electrically connecting the sensorelectronics (42) to a contact unit (34) that extends through thepackaging wall and that is connected to an electrical energy storage(50).
 8. The method according to claim 7, wherein: the contact unit (34)terminates in a pocket (32) of the packaging wall accessible from theoutside, and the method further comprising positioning the electricalenergy storage (50) in the pocket (32) after the sterilization step. 9.The method according to claim 7, wherein, after the connecting to theelectrical energy storage (50), the method further comprises:automatically reading an electrically readable dosimeter (D) comprisedby the sensor system (40), and then automatically writing a read-outdose value into the memory unit (44).
 10. The method according to any ofclaim 7, wherein, after the connecting to the electrical energy storage(50), the method further comprises: automatically periodically readingan electrically readable environmental parameter sensor (T, P, L)comprised by the sensor system (40), and then automatically writing intothe memory unit (44) correspondingly read-out parameter values togetherwith the corresponding reading time stamps.